Mechanism of Anti-urease Action by the Anti-ulcer Drug Ecabet Sodium.

Abstract

To investigate the mechanism of the anti-urease action of ecabet sodium (ecabet) observed in Helicobacter pylori in vitro, the effects of ecabet on purified urease from jack bean were studied in comparison with the effects of the specific urease inhibitor benzohydroxamic acid (BHA). After incubation of the enzyme with the test drug for a period of time, urease activity was measured. Ecabet depressed the activity below pH 5, and the lower the pH, the greater the degree of depression. The degree of depression by ecabet increased gradually during incubation and reached a plateau in 20 min, whereas that by BHA attained a maximum rapidly. The IC50 values of ecabet and BHA were 2.1 mg/ml and 0.5 microgram/ml, respectively. When the incubation mixture of urease with an inhibitor was diluted and further incubated, the depressed activity by BHA reverted gradually, but that by ecabet did not. When the incubation mixture of urease with ecabet was centrifuged, the urease activity of the mixture decreased in parallel with the reduction in protein concentration of the supernatant. When the incubation mixture of urease and 14C-ecabet was ultrafiltered to remove the drug, the radioactivity in the retentate remained in parallel with the degree of reduction of urease activity in the retentate. These results indicate that ecabet irreversibly depresses the urease activity of jack bean, and suggest that the depression is caused by irreversible binding of ecabet to urease followed by denaturation of the enzyme protein.

Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole‐based regimen

“…Recent studies have demonstrated that ecabet sodium has anti‐ H. pylori activity. In vitro studies have shown that ecabet sodium inhibits urease activity of H. pylori and adhesion to gastric epithelial cells 9 , . 10 , 24 In addition, ecabet sodium is reported to have suppressive activity on the growth of H. pylori in a dose‐dependent manner 12 .…”

“… 7 Ecabet sodium, which is a widely used cytoprotective agent for the gastric mucosa, is reported not only to have anti‐pepsin activity, but also to inhibit urease activity and growth of H. pylori. 8 –12 Several studies have shown that the addition of ecabet sodium increases the eradication rate of proton pump inhibitor‐based dual therapy for H. pylori infection 13 –16 . To our knowledge, the efficacy and safety of ecabet sodium‐based triple therapy with two antimicrobial agents has not yet been investigated.…”

High‐dose ecabet sodium improves the eradication rate of Helicobacter pylori in dual therapy with lansoprazole and amoxicillin

“…Urease is essential for H. pylori to live under acidic conditions 26 . Ecabet sodium irreversibly inhibits coarse urease derived from H. pylori at pH 5, which is the optimal pH for urease 27 –28 . Ecabet sodium also exhibited a dose‐dependent and rapid bactericidal effect against H. pylori in an acidic environment, although it had no effect on the viability of H. pylori in a neutral environment 29 .…”

Treatment of H. pylori Infection: A Review

“…tried to eradicate H. pylori, with disappointing results, with a long term assumption of probiotics shown to have a good inhibitory effect on H. pyori growth in vitro [134]. However, Ecabet sodium is an old antiulcer agent with demonstrated activity against H. pylori growth related to urease inhibition and reduction of the adhesion of bacteria on gastric mucosa [138][139][140][141]. It has been succesfully tested in H. pylori eradication, firstly in monkeys [142].…”